Data show that the circadian phase at which sleep and wakefulness occur can influence mood in both patients with mood disorders and in normal volunteers. The purpose of this project is to characterize the contributions of these sleep-wake and circadian effects to mood regulation in patients with rapid cycling bipolar disorder (RCBD), who experience at least four episodes of mania, hypomania, and/or depression in a year. The studies in this project include a cross-sectional study of sleep and hormonal secretion in hypomania and depression; naturalistic studies of the relationship between mood and sleep in patients with RCBD; and a forced desynchronization protocol. Results from the cross-sectional study show that the rhythms of melatonin, TSH, and cortisol vary with sleep timing and duration as the patients' moods cycle. Data from the naturalistic studies show that morning zeitgebers ("time-givers", entraining agents) and wake onset play a more significant role than evening zeitgebers and sleep onset in the pathophysiology of RCBD. In addition, these studies show a diurnal variation in the direction of mood switches in patients with RCBD, and demonstrate that there is no systematic relationship between menstrual cycle phase and mood in premenopausal women with RCBD. In the forced desynchronization protocol, patients are placed on a 28-hour day for thirteen days and frequent mood ratings are performed. Since the human circadian pacemaker cannot entrain to a 28-hour day, this protocol allows for the systematic dissociation of circadian and sleep-wake effects on mood.